Dataset Information

Transfer and Metabolism of the Xenoestrogen Zearalenone in Human Perfused Placenta.

ABSTRACT: BACKGROUND:Pregnancy is a sensitive condition during which adverse environmental exposures should be monitored thoroughly and minimized whenever possible. In particular, the hormone balance during gestation is delicate, and disturbance may cause acute or chronic long-term health effects. A potential endocrine disruption may be provoked by in utero exposure to xenoestrogens mimicking endogenous estrogens. The mycoestrogen zearalenone (ZEN), a toxic fungal secondary metabolite and mycotoxin found frequently in food and feed, constitutes a prominent example. OBJECTIVES:We performed a comprehensive assessment of the transfer as well as phase I and phase II metabolism of ZEN at the human placental barrier. METHODS:Human placentas were perfused with 1?M (318?g/L) ZEN for 6 h. Samples from the maternal and fetal compartment, placental tissue, and fetal plasma were analyzed by a highly sensitive UHPLC-MS/MS assay to detect ZEN as well as nine key metabolites (?-zearalenol, ?-zearalenol, zearalanone, ?-zearalanol, ?-zearalanol, ZEN-14-glucuronide, ?-zearalenol-14-glucuronide, ?-zearalenol-14-glucuronide, ZEN-14-sulfate). RESULTS:The model revealed a fast maternofetal transfer of ZEN across the human placental barrier. We also unraveled phase I and phase II metabolism of the parent toxin ZEN into the approximately 70-times more estrogenic ?-zearalenol and the less active ZEN-14-sulfate conjugate, which are effectively released into the maternal and fetal circulation in considerable amounts. CONCLUSIONS:Our findings suggest that exposure to ZEN (such as through consumption of ZEN-contaminated cereal-based products) during pregnancy may result in in utero exposure of the fetus, not only to ZEN but also some of its highly estrogenically active metabolites. In the light of the known affinity of ZEN and potentially co-occurring xenoestrogens to the estrogen receptor, and our results demonstrating placental transfer of ZEN and its metabolites in an ex vivo model, we recommend further research and more comprehensive assessment of gestational exposures in women. https://doi.org/10.1289/EHP4860.

SUBMITTER: Warth B

PROVIDER: S-EPMC6867367 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transfer and Metabolism of the Xenoestrogen Zearalenone in Human Perfused Placenta.

Warth Benedikt B Preindl Karin K Manser Pius P Wick Peter P Marko Doris D Buerki-Thurnherr Tina T

Environmental health perspectives 20191009 10

<h4>Background</h4>Pregnancy is a sensitive condition during which adverse environmental exposures should be monitored thoroughly and minimized whenever possible. In particular, the hormone balance during gestation is delicate, and disturbance may cause acute or chronic long-term health effects. A potential endocrine disruption may be provoked by <i>in utero</i> exposure to xenoestrogens mimicking endogenous estrogens. The mycoestrogen zearalenone (ZEN), a toxic fungal secondary metabolite and m ...[more]

PMID: 31596610

Similar Datasets

Project description:The mycotoxin zearalenone (ZEN) is a frequent contaminant of animal feed and is well known for its estrogenic effects in animals. Cattle are considered less sensitive to ZEN than pigs. However, ZEN has previously been shown to be converted to the highly estrogenic metabolite α-zearalenol (α-ZEL) in rumen fluid in vitro. Here, we investigate the metabolism of ZEN in the reticulorumen of dairy cows. To this end, rumen-fistulated non-lactating Holstein Friesian cows (n = 4) received a one-time oral dose of ZEN (5 mg ZEN in 500 g concentrate feed) and the concentrations of ZEN and ZEN metabolites were measured in free rumen liquid from three reticulorumen locations (reticulum, ventral sac and dorsal mat layer) during a 34-h period. In all three locations, α-ZEL was the predominant ZEN metabolite and β-zearalenol (β-ZEL) was detected in lower concentrations. ZEN, α-ZEL and β-ZEL were eliminated from the ventral sac and reticulum within 34 h, yet low concentrations of ZEN and α-ZEL were still detected in the dorsal mat 34 h after ZEN administration. In a second step, we investigated the efficacy of the enzyme zearalenone hydrolase ZenA (EC 3.1.1.-, commercial name ZENzyme®, BIOMIN Holding GmbH, Getzersdorf, Austria) to degrade ZEN to the non-estrogenic metabolite hydrolyzed zearalenone (HZEN) in the reticulorumen in vitro and in vivo. ZenA showed a high ZEN-degrading activity in rumen fluid in vitro. When ZenA was added to ZEN-contaminated concentrate fed to rumen-fistulated cows (n = 4), concentrations of ZEN, α-ZEL and β-ZEL were significantly reduced in all three reticulorumen compartments compared to administration of ZEN-contaminated concentrate without ZenA. Upon ZenA administration, degradation products HZEN and decarboxylated HZEN were detected in the reticulorumen. In conclusion, endogenous metabolization of ZEN in the reticulorumen increases its estrogenic potency due to the formation of α-ZEL. Our results suggest that application of zearalenone hydrolase ZenA as a feed additive may be a promising strategy to counteract estrogenic effects of ZEN in cattle.

Dataset Information

Transfer and Metabolism of the Xenoestrogen Zearalenone in Human Perfused Placenta.

Publications

Transfer and Metabolism of the Xenoestrogen Zearalenone in Human Perfused Placenta.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets